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Venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) is a common disorder, which is estimated to affect 900,000 patients each year in the United States. Approximately one-third of these cases are fatal pulmonary emboli, and the remaining two-thirds are nonfatal episodes of symptomatic deep vein thrombosis or pulmonary embolism. The majority of fatal events occur as sudden or abrupt death, underscoring the importance of prevention as the critical strategy for reducing death from pulmonary embolism. Of the estimated 600,000 cases of nonfatal venous thromboembolism each year, approximately 60 percent present clinically as deep vein thrombosis and 40 percent present as pulmonary embolism. Most clinically important pulmonary emboli arise from proximal deep vein thrombosis (thrombosis involving the popliteal, femoral, or iliac veins). Upper extremity deep vein thrombosis also may lead to clinically important pulmonary embolism. The clinical features of deep vein thrombosis and pulmonary embolism are nonspecific. Objective diagnostic testing is required to confirm or exclude the presence of venous thromboembolism. An appropriately validated assay for plasma D-dimer, if available, provides a simple, rapid, and cost-effective first-line exclusion test in patients with low, unlikely, or intermediate clinical probability. Compression ultrasonography of the proximal veins performed at presentation, and if normal, repeated once 5 to 7 days later, can safely exclude clinically important deep vein thrombosis in symptomatic patients. In centers with the expertise, a single comprehensive evaluation of the proximal and calf veins with duplex ultrasonography is sufficient. If capability for combined computed tomographic angiography (CTA) and computed tomographic venography (CTV) exists, it is the preferred approach for most patients with suspected pulmonary embolism because it provides a definitive basis to give or withhold antithrombotic therapy in 90 percent of patients. CTA is not inferior to using ventilation–perfusion lung scanning for excluding the diagnosis of pulmonary embolism when either test is used together with venous ultrasonography of the legs. Anticoagulant therapy is the preferred treatment for most patients with acute venous thromboembolism. Initial treatment with subcutaneous low-molecular-weight heparin or fondaparinux, followed by long-term treatment with an oral vitamin K antagonist such as warfarin sodium, is effective for preventing recurrent venous thromboembolism. Use of low-molecular-weight heparin or fondaparinux enables outpatient therapy and is the preferred initial therapy for most patients. Treatment with low-molecular-weight heparin for at least 6 months is preferred in cancer patients and should be continued if cancer is not resolved. Thrombolytic therapy is indicated for patients with pulmonary embolism who present with cardiovascular collapse and in selected patients who have impaired right ventricular function. Insertion of a vena cava filter is indicated for patients who have an absolute contraindication to anticoagulant therapy or who have recurrent venous thromboembolism despite adequate anticoagulant treatment. Anticoagulant treatment should be continued for at least 3 months in patients with a first episode of venous thromboembolism secondary to a reversible risk factor. Indefinite anticoagulant therapy should be considered for patients with idiopathic venous thromboembolism, certain thrombophilias, or recurrent venous thromboembolism.

Acronyms and Abbreviations

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